Abstract:
:Cancer-associated fibroblasts (CAFs) promote tumour invasion and metastasis. We show that CAFs exert a physical force on cancer cells that enables their collective invasion. Force transmission is mediated by a heterophilic adhesion involving N-cadherin at the CAF membrane and E-cadherin at the cancer cell membrane. This adhesion is mechanically active; when subjected to force it triggers β-catenin recruitment and adhesion reinforcement dependent on α-catenin/vinculin interaction. Impairment of E-cadherin/N-cadherin adhesion abrogates the ability of CAFs to guide collective cell migration and blocks cancer cell invasion. N-cadherin also mediates repolarization of the CAFs away from the cancer cells. In parallel, nectins and afadin are recruited to the cancer cell/CAF interface and CAF repolarization is afadin dependent. Heterotypic junctions between CAFs and cancer cells are observed in patient-derived material. Together, our findings show that a mechanically active heterophilic adhesion between CAFs and cancer cells enables cooperative tumour invasion.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Labernadie A,Kato T,Brugués A,Serra-Picamal X,Derzsi S,Arwert E,Weston A,González-Tarragó V,Elosegui-Artola A,Albertazzi L,Alcaraz J,Roca-Cusachs P,Sahai E,Trepat Xdoi
10.1038/ncb3478subject
Has Abstractpub_date
2017-03-01 00:00:00pages
224-237issue
3eissn
1465-7392issn
1476-4679pii
ncb3478journal_volume
19pub_type
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